P976: BENDAMUSTINE-POMALIDOMIDE-DEXAMETHASONE (BPD) FOR RELAPSED AND/OR REFRACTOR MULTIPLE MYELOMA WITH EXTRAMEDULLARY DISEASE
Authors: Z. Yuping, H. Y. Wu, X. Chu, X. Deng, X. Feng, C. Yuan, X. Ran, G. Liu, C. Fan, H. Hao, X. Zhou
Journal: HemaSphere (2022)

Background: Extramedullary disease (EMD) is a rare manifestation of multiple myeloma (MM). The incidence is about 6-20% in the relapsed MM patients. Although novel agents prolong the survival of patients with MM, patients with EMD are prone to relapse or progress again easily,EMD may be associated with decreased overall survival in MM. No standard therapy has been established for this high-unmet need population. Bendamustine is an old bi-functional alkylating agent which has proved to be effective in Multiple Myeloma (MM). Pomalidomide is a potent immunomodulatory drug agent with anti-angiogenic, anti-proliferative, and immunomodulatory activity against MM. Preclinical studies showed that bendamustine and pomalidomide had higher penetration rate of cerebrospinal fluid. In China, the price of two drugs is relatively economical. In a phase I/II study,the combination of BPd demonstrates deep Response(ORR:61%) and has a favorable tolerance profile in patients with RRMM. To summarize,BPD is an safe,effective, and economical treatment, and there are no studies of BPD in the regimen of RRMM with EMD,so it is worth exploring in domestic clinical trials. Aims: To evaluate the efficacy and safety of bendamustine, Pomalidomide, and dexamethasone (BPd) for relapsed / refractor multiple myeloma with EMD. Methods: This is an open-label, multicenter, prospective study(ChiCTR2100048829).Eligible patients were aged≥18 years, and had a diagnosis of RRMM with EMD, and an Eastern Cooperative Oncology Group performance status of 0-2,Patients received bendamustine 75 mg/m2 on days 1 and 2(If there is no severe side effects in the first cycle, it can be increased to 80mg/m2), 6 cycles. Pomalidomide 4 mg on days 1-21,until progression or intolerable toxicity. Dexamethasone 20mg on days1-4, 15-18, until progression or unacceptable toxicity. Each cycle is 28days. The primary endpoint is overall response rates (ORR). Results: A total of 21 patients were enrolled in the study,12(57.14%) patients with first relapse multiple myeloma. The median age is 57.4years(47-72). According to IMWG criteria, all first relapse patients responded(ORR100%)and CR:3pts(25%),VGPR:7pts(58.33%),PR:2pts(16.67%).Patients with ≥2nd relapese, the ORR was44.44%,≥VGPR:0pts(0%), PR:4pts(44.44%),SD:3pts (33.33%),PD:2pts(22.22%).This results established that BPD has a deep Response in first relapse MM with EMD.The 1-year PFS was79.16%of all patients.The most common grade 3 or 4 hematologic toxicities were neutropenia7(33.33%),thrombocytopenia4(19.05%),anemia 2(9.52%). Overall,the severe toxicities are manageable. Table 1. - Patient characteristics Age, years, median (range) 57.4(47-72) ECOG performance status(n,%) ISS disease stage(n,%) Number of prior therapies,median (range)(n,%) 0 4 19.05% I 2 9.52% 1 12 57.14% 1 10 47.62% II 3 14.29% ≥1 9 42.86% 2 7 33.33% III 16 76.19% Table 2. - International Myeloma Working Group best response IMWG first relapse(n,%) ≥2nd relapese(n,%) ALL(n,%) ORR 12 100.00% 4 44.44% 16 76.19% SCR 0 0.00% 0 0.00% 0 0.00% CR 3 25.00% 0 0.00% 3 14.29% VGPR 7 58.33% 0 0.00% 7 33.33% PR 2 16.67% 4 44.44% 6 28.57% SD 0 0.00% 3 33.33% 3 14.29% PD 0 0.00% 2 22.22% 2 9.52% Image:Summary/Conclusion: Safety data from the study demonstrates that BPD regimen has a favorable tolerance profile in patients for RRMM with EMD. Early efficacy is encouraging, Longer-term results still require more patients have been enrolled and further follow-up. The combination of BPD will be an effective treatment strategy in RRMM with EMD.